Histone acetyltransferases (HATs) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF family of scaffold proteins. Their plant homeodomain (PHD)-Zn knuckle-PHD domain is essential for binding chromatin and is restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region to the N terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity between H4 and H3 tails. These results uncover a crucial new role for associated proteins within HAT complexes, previously thought to be intrinsic to the catalytic subunit.

We present a complete analysis of the structure of polyethylene (PE) nanoparticles synthesized and stabilized in water under very mild conditions (15°C, 40 atm) by a nickel-catalyzed polymerization in aqueous solution. Combining cryogenic transmission electron microscopy (cryo-TEM) with X-ray scattering, we demonstrate that this new synthetic route leads to a stable dispersion of individual PE nanoparticles with a narrow size distribution. Most of the semicrystalline particles have a hexagonal shape (lateral size 25 nm, thickness 9 nm) and exhibit the habit of a truncated lozenge. The combination of cryo-TEM and small-angle X-ray scattering demonstrates that the particles consist of a single crystalline lamella sandwiched between two thin amorphous polymer layers ("nanohamburgers"). Hence, these nanocrystals that comprise only ca. 14 chains present the smallest single crystals of PE ever reported. The very small thickness of the crystalline lamella (6.3 nm) is related to the extreme undercooling (more than 100°C) that is due to the low temperature at which the polymerization takes place. This strong undercooling cannot be achieved by any other method so far. Dispersions of polyethylene nanocrystals may have a high potential for a further understanding of polymer crystallization as well as for materials science as, e.g., for the fabrication of extremely thin crystalline layers.Polyethylene (PE) is a commodity polymer that has become ubiquitous over the past several decades because of its low price and good mechanical properties. 1 Hence, the number of applications of the material is huge and many millions of tons are produced worldwide annually. However, PE has hardly played any role in the field of nanotechnology. This is due to the problem that PE is produced either by free radical polymerization under high pressure and temperature or with metal-organic catalysts working exclusively under strictly water-free conditions. Polymer nanoparticles and their composites with inorganic compounds, however, are very often produced in aqueous systems. 2 Recently, it was demonstrated that ethylene can be polymerized in aqueous systems in a catalytic fashion by Ni(II) complexes. [3][4][5][6] By virtue of this novel synthesis, long chains of polyethylene can be generated in a well-controlled environment and at ambient temperature. Thus, it could be shown that aqueous PE dispersions can be produced. This novel way of polymerization hence opens the way for the creation of nanostructures made from PE. Up to now, the particles synthesized in this way were semicrystalline and for the largest part consisted of stacks of several crystalline lamellae. 6

SUMMARY Death Inducer Obliterator 3 (Dido3) is implicated in the maintenance of stem cell genomic stability and tumorigenesis. Here, we show that Dido3 regulates the expression of stemness genes in embryonic stem cells through its plant homeodomain (PHD) finger. Binding of Dido3 PHD to histone H3K4me3 is disrupted by threonine phosphorylation that triggers Dido3 translocation from chromatin to the mitotic spindle. The crystal structure of Dido3 PHD in complex with H3K4me3 reveals an atypical aromatic-cage-like binding site that contains a histidine residue. Biochemical, structural, and mutational analyses of the binding mechanism identified the determinants of specificity and affinity and explained the inability of homologous PHF3 to bind H3K4me3. Together, our findings reveal a link between the transcriptional control in embryonic development and regulation of cell division.

Dopamine (DA) is an important neurotransmitter associated with nerve signaling and some diseases. Therefore, it is very significant to detect DA in patients to regulate body function. Compared with other traditional methods, these electrochemical sensors have their intrinsic advantages of high sensitivity, celerity, simplicity, and economy. In this article, a graphene quantum dots/multiwalled carbon nanotubes (GQDs-MWCNTs) composite-based ultrasensitive electrochemical sensor for detecting dopamine (DA) was fabricated. As the carbon nanomaterials, GQDs have large surface areas to improve the conductivity of the electrodes, and the MWCNTs are excellent electrode materials. As expected, the sensor has excellent selectivity of dopamine among other interfering bioanalytes. Under optimum conditions, this electrochemical sensor exhibited maximum performance toward DA determination with good linearity in a broad linear range of 0.005 to 100.0 μM with the detection limit of 0.87 nM (3S/N). Furthermore, this electrochemical sensor was successfully applied for detecting DA in human serum, and it was the first example to measure DA secreted from live PC12 cells with excellent performance.

The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-Å resolution crystal structure of MLL5 plant homeodomain in complex with the H3K4me3 peptide reveals a noncanonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a unique His-Asp swapping rearrangement mediated by a C-terminal α-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is conserved in the Drosophila ortholog of MLL5, UpSET, and suggests the developmental control for targeting of H3K4me3. Together, our findings provide first insights into the molecular basis for the recruitment, exclusion, and regulation of MLL5 at chromatin.T he mixed-lineage leukemia 5 (MLL5) protein was initially identified as a candidate tumor suppressor and more recently has been shown to play a critical role in hematopoiesis and lymphopoiesis (1). The MLL5 gene-containing region of chromosome 7 is frequently deleted in patients with hematological disorders, including acute myeloid and therapy-induced leukemias and myeloid dysplastic syndrome (MDS). Depletion of Mll5 in mice causes mild postnatal lethality, with some of the surviving animals showing retarded growth, male sterility, and decreased size of thymus, spleen, and lymph nodes (2-4). Genetic analyses of these Mll5 deficiencies reveals a 30% decrease in the number of hematopoietic stem cells (HSC) and progenitors, defects in HSC self-renewal mechanisms, and impaired myeloid differentiation (2-4). In addition to being an essential mediator of HSC homeostasis, MLL5 has been implicated in cytokinesis, the DNA damage response, and genome maintenance (5-7). Overexpression and knockdown of MLL5 both induce cell cycle arrest at various phases, suggesting a versatile function of MLL5 throughout the cell cycle (5).MLL5 belongs to the MLL family of methyltransferases that regulate gene expression during developmental processes. These enzymes catalyze the addition of methyl groups to the e-amino moiety of lysine and are highly specific for lysine 4 of histone H3. Along with MLL5, also known as a lysine methyltransferase 2E (KMT2E), the MLL family contains MLL1-4, SET1A, and SET1B (KMT2A-KMT2D, KMT2F, and KMT2G, respectively) (8). Full-length MLL5 is ∼200 kDa and is evolutionarily distant from the more canonical and better-characterized members of this family. Unlike the other multimodular MLL proteins, MLL5 consists of only two conserved motifs near the N terminus, a plant homeodomain (PHD) finger, followed by a catalytic Su(var)3-9, enhancer of zeste, trithorax (SET) domain. A long, ∼1,000-residue C-terminal region of MLL5 displays no apparent homology to...

The recent progress in blue-emitting organic electrofluorescence materials with high performance using triplet excitons is reviewed.

We study the change of the size and structure of freely suspended single lamella nanoparticles of polyethylene during thermal annealing in aqueous solutions. Using small-angle x-ray scattering and cryogenic transmission electron microscopy, it is shown that a doubling of the crystalline lamella sandwiched between two amorphous polymer layers is obtained by annealing the nanoparticles at 125 • C. This thickening of the crystalline lamella can be understood in terms of an unlooping of polymer chains within a single nanoparticle. In addition a variation of the annealing temperature from 90 • C to 115 • C demonstrates that the inverse of the crystalline lamellar thickness increases linearly with the annealing temperatures leading to a recrystallization line in a Gibbs-Thomson graph. Since the nanoparticles consist of about only eight polymer chains, they can be considered as a ideal candidates for the experimental realization of equilibrium polymer crystals.

A series of bipolar phenanthroimidazole derivatives, TTP-TPI, DPT-TPI, and DPF-TPI, were designed and synthesized by incorporating polyaromatic hydrocarbon groups to phenanthroimidazole through a phenyl bridge. The bulky polyaromatic hydrocarbon units endow the molecules with high glass-transition temperatures, nonplanar twisty structures which reduce molecular aggregations. The bipolar transporting natures of these materials are demonstrated by single-carrier devices with supported of theoretical calculations. Nondoped organic light-emitting devices (OLEDs) using these phenanthroimidazole derivatives as emitters show blue-violet to sky-blue emissions with Commission Internationale de l’Eclairage (CIE) coordinates of (0.16, 0.05) for TTP-TPI, (0.16, 0.07) for DPT-TPI, and (0.17, 0.24) for DPF-TPI. The TTP-TPI-, DPT-TPI-, and DPF-TPI-based nondoped devices show impressive external quantum efficiencies (EQE) of 5.02, 5.25, 4.85%, respectively (corresponding current efficiencies: 2.10, 3.13, and 8.41 cd/A). These values are the best or among the best comparing to those of the reported nondoped OLEDs with the corresponding color gamuts. These devices also show small efficiency roll-off at high brightness (1000 cd/m2) with EQEs drop by 20.7, 12, and 0%. Moreover, with well-balanced carrier transport, DPF-TPI based device can achieve a higher brightness of 10000 cd/m2 with EQE maintaining at 4.49% (only drop by 7.4%).